Bevacizumab Treatment of Radiation-Induced Brain Necrosis: A Systematic Review

Abstract

BackgroundRadiation brain necrosis (RBN) is a serious complication in patients receiving radiotherapy for intracranial disease. Many studies have investigated the efficacy and safety of bevacizumab in patients with RBN. In the present study, we systematically reviewed the medical literature for studies reporting the efficacy and safety of bevacizumab, as well as for studies comparing bevacizumab with corticosteroids.Materials and MethodsWe searched PubMed, Cochrane library, EMBASE, and ClinicalTrials.gov from their inception through 1 March, 2020 for studies that evaluated the efficacy and safety of bevacizumab in patients with RBN. Two investigators independently performed the study selection, data extraction, and data synthesis.ResultsOverall, the present systematic review included 12 studies (eight retrospective, two prospective, and two randomized control trials [RCTs]) involving 236 patients with RBN treated who were treated with bevacizumab. The two RCTs also had control arms comprising patients with RBN who were treated with corticosteroids/placebo (n=57). Radiographic responses were recorded in 84.7% (200/236) of patients, and radiographic progression was observed in 15.3% (36/236). Clinical improvement was observed in 91% (n=127) of responding patients among seven studies (n=113). All 12 studies reported volume reduction on T1 gadolinium enhancement MRI (median: 50%, range: 26%–80%) and/or T2 FLAIR MRI images (median: 59%, range: 48%–74%). In total, 46 responding patients (34%) had recurrence. The two RCTs revealed significantly improved radiographic response in patients treated with bevacizumab (Levin et al.: p = 0.0013; Xu et al.: p < 0.001). Both also showed clinical improvement (Levin et al.: NA; Xu et al.: p = 0.039) and significant reduction in edema volume on both T1 gadolinium enhancement MRI (Levin et al.: p=0.0058; Xu et al.: p=0.027) and T2 FLAIR MRI (Levin et al.: p=0.0149; Xu et al.: p < 0.001). Neurocognitive improvement was significantly better after 2 months of treatment in patients receiving bevacizumab than in those given corticosteroids, as assessed by the MoCA scale (p = 0.028). The recurrence rate and side effects of the treatments showed no significant differences.ConclusionsPatients with RBN respond to bevacizumab, which can improve clinical outcomes and cognitive function. Bevacizumab appears to be more efficacious than corticosteroid-based treatment. The safety profile was comparable to that of the corticosteroids.

Bevacizumab Combined with Corticosteroids Does Not Improve the Clinical Outcome of Nasopharyngeal Carcinoma Patients With Radiation-Induced Brain Necrosis

“…The treatment of RN is a challenging issue as the number of RN patients has gone up with the widespread application of radiotherapy over the last decades. Corticosteroids and bevacizumab are the two main recommended treatments ( 13 , 14 ). Corticosteroids are the first-line treatment for RN.…”

“…Corticosteroids are the first-line treatment for RN. A recent review summarized that bevacizumab was more efficacious than corticosteroid treatment ( 13 ). Interestingly, our study found that the treatment strategy combining bevacizumab with corticosteroids did not lead to better clinical outcomes for NPC patients with RN.…”

“…The following demographic and clinical characteristics were recorded: sex, age, clinical symptoms, total radiation dose of the brain and neck, radiotherapy approaches [conventional vs. intensity-modulated radiation therapy (IMRT)], duration between radiotherapy and RN diagnosis (DRRN), duration between radiotherapy and bevacizumab treatment (DRT), duration between RN diagnosis and bevacizumab treatment (DRNT), RN treatment strategy, the location of the RN lesion, and the RN volume on MRI at baseline and during follow-up (10,11). Quality of life assessed by the abbreviated World Health Organization Quality of Life (WHOQOL-BREF) scale ( 12) and cognitive function assessed by the Montreal Cognitive Assessment (MoCA) scale were also collected at baseline and post-treatment (13).…”

Review: Neurological Complications From Therapies for Pediatric Brain Tumors

“…For patients requiring longer term treatment, bevacizumab (an anti-vascular endothelial growth factor (VEGF) monoclonal antibody) has demonstrated robust clinical and radiographic response in multicenter prospective trials, avoiding steroid-treatment toxicity ( 61 , 62 ). Bevacizumab has also shown significant improvement in neurocognitive outcomes, including attention, language, concentration, memory, visuospatial orientation, and calculation at two months compared to patients treated with corticosteroids only ( 63 ). However, as an anti-angiogenesis agent, bevacizumab decreases wound healing and predisposes patients to hemorrhage and thrombosis.…”

“…Extrinsic factors consist of physical and biological barriers preventing trafficking of therapies into the intracranial space, such as the blood brain barrier and tumor microenvironment ( 65 ). For immunotherapies like CAR T-cell and virotherapies, intrinsic limitations such as limited targetable tumor antigens, insufficient proliferation or expansion and lack of durable response can also hinder clinical efficacy ( 63 ). Brain tumors, especially gliomas, can circumvent the binding and targeting of these novel therapies by upregulating expression of inhibitory ligands and cytokines, and downregulating targeted tumor antigens, preventing recognition by CAR T-cells, viral vectors, and avoiding check point inhibition ( 68 , 69 ).…”